Field of the Invention
The present invention relates to the field of chemistry. More particularly, embodiments of the invention provide regioselectively substituted carbohydrate and polysaccharide derivatives, such as cellulose esters, and methods for preparing them.
Description of Related Art
Cellulose is one of the most abundant natural polymers on earth, consisting of unsubstituted, unbranched β(1→4) linked D-glucose units:

Cellulose comprises several thousand glucose units linked in a linear fashion. The chains are stabilized by intramolecular and intermolecular hydrogen bonds (shown as the dashed lines in the structure provided above). Cellulose esters can be prepared by reacting the hydroxyl groups of cellulose with acids or other acylating agents. Less than fully substituted cellulose esters (i.e., having a degree of substitution (DS) of less than 3) are used in various applications. For example, such compounds find use in molding plastics, clear sheets, filter tow, and as coatings polymers. In particular, acetylation with acetic acid or acetic anhydride produces a variety of different products with properties that depend on the degree of substitution.
It has been found that regioselectivity of substitution can have a strong impact on the physical properties of the resultant compounds. For example, solubility, optical properties, thermal properties, and crystallinity have all been shown to be strongly dependent on regioselectivity. See Kondo, T. J., Polym. Sci., Part B: Polym. Phys. 1997, 35, 717; and see Fox, S. C.; Edgar, K. J., Cellulose 2011, 18, 1305; and see Buchanan, C. M.; Buchanan, N. L.; Guzman-Morales, E., “Control of regioselectivity during esterification of cellulose”, CELL-10, Abstracts of Papers, American Chemical Society National Meeting, San Francisco, Calif., United States, Mar. 21-25, 2010; and see Iwata, T.; Fukushima, A.; Okamura, K.; Azuma, J., J. Appl. Polym. Sci. 1997, 65, 1511; and see Iwata, T.; Okamura, K.; Azuma, J.; Tanaka, F., Cellulose 1996, 3, 91; and see Iwata, T.; Okamura, K.; Azuma, J.; Tanaka, F., Cellulose 1996, 3, 107. The ability to prepare cellulose esters having a high degree of control over the position of substitution is, however, a very difficult problem in organic chemistry, polymer science, analytical chemistry, and materials science.
The paucity of general solutions to this problem is a limiting factor in the development of novel materials from renewable cellulose, which are an important part of a biorefinery-based economy. See Edgar, K. J.; Buchanan, C. M.; Debenham, J. S.; Rundquist, P. A.; Seiler, B. D.; Shelton, M. C.; Tindall, D., Prog. Polym. Sci. 2001, 26, 1605; and see Klemm, D.; Heublien, B.; Fink, H.-P.; Bohn, A., Angew. Chem., Int. Ed. 2005, 44, 3358; and see Fox, S. C.; Li, B.; Xu, D.; Edgar, K. J., Biomacromolecules 2011, 12, 1956 (“Fox 1956”). Thus, it is of great interest to develop new synthetic pathways for regioselectively substituted cellulose esters, which is crucial for understanding their structure-property relationships and design of cellulose derivatives with unique properties, like crystallinity, thermal properties, solubility, and optical properties. See Iwata, T., Okamura, K., Azuma, J. Tanaka, F., Cellulose 1996, 3; and see Iwata, T., Okamura, K., Azuma, J. Tanaka, F., Cellulose 1996, 3; and see Iwata, T., Fukushima, A., Okamura, K., Azuma, J., J. Appl. Polym. Sci. 1997, 65; and see Kondo, T., J. Polym. Sci., Part B: Polym. Phys. 1994, 32; and see Buchanan, C. M. B., N. L.; Guzman-Morales, E.; Wang, B., “Control of regioselectivity during esterification of cellulose”, CELL-10, Abstracts of Papers, ACS National Meeting, San Francisco, Calif., United States, Mar. 21-25, 2010.
In light of the low reactivity of cellulosic hydroxyl groups resulting from the hydrogen and hydrophobic bonding, poor solubility, and steric hindrance, it is quite challenging to synthesize regioselectively substituted cellulose esters. Modern cellulose solvent systems, such as LiCl/N, N-dimethylacetamide (DMAc), dimethylsulfoxide (DMSO)/tetrabutylammonium fluoride trihydrate (TBAF, which can include the trihydrate), and ionic liquids, enhance the cellulosic OH reactivity by breaking up the extensive hydrogen bonding. See Liebert, T., Heinze, T., Biomacromolecules 2005, 6, 333, see Edgar, K. J., Arnold, K. M., Blount, W. W., Lawniczak, J. E., Lowman, D. W. Macromolecules 1995, 28, pp 4122-4128, see Kohler, S., Heinze, T. Macromolecular Bioscience 2007, 7, 307, and see El Seoud, O., A. Koschella, A., Fidale, L. C., Dorn, S., Heinze, T. Biomacromolecules 2007, 8, 2629. The relatively small reactivity differences between the 2-, 3-, and 6-OH groups, however, make selectivity very difficult to achieve, especially for esterification reactions, in which direct esterification of cellulose with sterically demanding acylating reagents provided only modest selectivity on 6-OH. See Xu, D., Li, B., Tate, C., Edgar, K. J. Cellulose 2011, 18, pp 405-419.
It is believed that the difficulty of regioselective substitution arises because of the low reactivity of cellulosic hydroxyls towards electrophiles, due to the restricted steric access, mobility, and wetting imposed by the linear, hydrophilic cellulose polymer structure. Often aggressive reaction conditions are required to drive reactions like esterification and etherification. The resulting necessity of using strong catalysts, high temperatures, and/or large molar excesses of reagents is not conducive to selectivity.
The advent of solvents for cellulose has facilitated the first significantly regioselective syntheses of cellulose ethers and esters, by permitting the use of milder reaction conditions and reagents. Protection/deprotection chemistry is one of the most common strategies for the synthesis of regioselectively substituted cellulose derivatives. Prior attempts to synthesize cellulose esters with high regioselectivity have involved the use of protective groups, which can significantly reduce overall yield, require high chemo- and regioselectivity in each of several steps, and can themselves reduce the reactivity of cellulose and impede succeeding reactions, as well as increase overall cost. See Fox 1956.
One of the few most interesting solvents for modification of cellulose has been dimethylsulfoxide (DMSO) containing tetrabutylammonium fluoride (TBAF). See Kohler, S.; Heinze, T., Macromol. Biosci. 2007, 7, 307. DMSO/TBAF dissolves cellulose faster and under milder conditions (room temperature, 15 min for degree of polymerization (DP)<650) than any other cellulose solvent. Cellulose ether synthesis in DMSO/TBAF is effective, but several researchers have noted that the synthesis of cellulose esters in this solvent is of limited scope due to the low degree of substitution (DS) of the products obtained. See Ramos, L. A.; Frollini, E.; Heinze, T., Carbohydr. Polym. 2005, 60, 259; and see Ass, B. A.; Frollini, E.; Heinze, T., Macromol. Biosci. 2004, 4, 1008; and see Xu, D.; Li, B.; Tate, C.; Edgar, K. J., Cellulose 2011, 18, 405; and see Hussain, M. A.; Liebert, T.; Heinze, T., Macromol. Rapid Commun. 2004, 25, 916. It is believed that TBAF is roughly a trihydrate and that reaction of the waters of hydration (in preference to cellulose) with the acylating reagent is cited as the probable cause of low DS ester products. What is more, the TBAF trihydrate is difficult to break by drying processes and attempts to do so result in β-elimination reactions of the TBA (tetrabutylammonium) moiety, degrading the TBAF salt. See Sun, H.; DiMagno, S. G. J. Am. Chem. Soc. 2005, 127, 2050.
Close examination of the literature has revealed a few hints of the possibility of fluoride-catalyzed deacylation. For example, Bunton and Fendler investigated the catalysis of acetic and propionic anhydride hydrolyses by fluoride ion (NaF or KF). See Bunton, C. A., Fendler, J. H., “Fluoride Ion Catalyzed Hydrolysis of Carboxylic Anhydrides,” J. Org. Chem. May 1967, 32, 1547-1551. They presented evidence that the observed rate acceleration was due to general base catalysis, rather than nucleophilic attack by F− to generate acetyl fluoride. In 1991 Rinehart and co-workers reported the deacylation of amino acids and peptides containing benzyl and nitrobenzyl ester protecting groups. See Namikoshi, M.; Kundu, B.; Rinehart, K. L., “Use of Tetrabulylammonium Fluoride as a Facile Deprotecting Reagent for 4-Nitrobenzyl,2,2,2-Trichloroethyl, and Phenacyl Esters of Amino Acids, J. Org. Chem. 1991, 56, 5464-5466. They found that TBAF not only catalyzed deacylation, but also provided chemoselectivity, deacylating 4-nitrobenzyl esters selectively in the presence of benzyl esters.
Even further, Ueki and co-workers observed deacylation of phenacyl esters by TBAF and, in the presence of thiols, benzoate esters as well. See Ueki, M., Aoki, H., Katoh, T., “Selective Removal of Phenacyl Ester Group with a TBAF.xH2O-Thiol System from Amino Acid Derivatives Containing Benzyl or 4-Nitrobenzyl Ester,” Tet. Lett. 1993, Vol. 34, No. 17, 2783-2786. Although El Seoud and co-workers published a fascinating study that reported the deacylation of cellulose acetate and other cellulose esters catalyzed by tetraallylammonium fluoride in DMSO solvent, see Casarano, R., Nawaz, H., Possidonio, S., da Silva, V. i. C., El Seoud, O. A., “A Convenient Solvent System for Cellulose Dissolution and Derivatization: Mechanistic Aspects of the Acylation of the Biopolymer in Tetraallylammonium Fluoride/Dimethyl Sulfoxide,” Carbohydr. Polym., 86 (2011), 1395-1402, these authors did not report the observation of any regioselectivity in this deacylation reaction, and they attributed the deacylation to nucleophilic attack by F− with acetyl fluoride generation.
Thus, it can be seen that having efficient methods of making highly regioselectively substituted cellulose esters will enable structure-property studies that identify optimal material performance in particular applications, supply the materials to deliver that optimal performance, and facilitate the understanding of analytical characteristics of particular cellulose ester regioisomers that will enable better control of traditional synthesis processes.